[MUSIC] [MUSIC] Hello then welcome back again Cortisol affects almost every system in the body. It literally integrates the body and the mind, by altering the configuration of the brain. Some of the genes turned on by cortisol are important for freeing stored energy, which helps with both fighting and fleeing. But too much cortisol over a long period can lead to heart disease, depression and increased susceptibility to infection. Because cortisol suppresses the immune system. You may remember from last week's lectures that for our species, social isolation is incredibly toxic. Mucks up our immune system. Cortisol probably has a lot to do with this. So that's also why people stressing over passing an exam, are more likely to catch colds, and unhappy nurses have more cold sores, and anxious people. Have more outbreaks of genital herpes. And cortisol does what it does by switching on or off genes. But it only affects genes and cells that have cortisol receptors in them. It's the cortisol-receptor complex, acting together, that binds to genes and turns them on. Cortisol is a steroid hormone. You may remember that I mentioned another steroid hormone, testosterone, in a previous lecture. Now, being made of lipid, cortisol and testosterone can pass through the plasma membrane, which is also made of lipid. So it's just like one fat dissolving into another. Cortisol and testosterone are both simple little molecules easily made from cholesterol. And as you can see from this figure, they're both very similar in shape. It wouldn't do, would it, if a cell got confused between them. Testosterone is the hormone that tells cells they're in a masculine body. Cortisol means you're under attack, or for some other reason, having stressful thoughts. The price you pay for having simple, cheaply-made hormones is that the cortisol and testosterone receptors need to be very sophisticated, so they can recognize their own hormones and not mix them up. Now look at this figure. This is how the system works. The steroid hormone passes through the plasma membrane. And if the cell has the right receptor in it, then the hormone's going to bind to its receptor. In this case, cortisol, cortisol binds to its receptor. The complex specifically recognizes and attaches the DNA sequences in the promoters of stress-related genes, and switches them on. So you get stress-related proteins being produced. And many of these proteins, in their turn, switch on other genes. And sometimes these genes, too, will produce proteins to switch on other genes. So directly or indirectly, cortisol can switch on hundreds of genes. What this tells us is that though you are clearly assembled from proteins encoded by your genes, how and when a lot of those genes get switched on is going to depend on what happens to you in your life. External events or free will behavior can switch on genes. Being frightened at a movie can switch on genes. And bear in mind, environment doesn't begin at birth. The shared environment between you and your mother can also have long-term consequences. For nine months, you shared a very intimate environment with your mother's circulatory system. Where is the fetus getting its nutrition, its hormones and oxygen from? The mother. A female rat gets stressed. Bad things happening in the environment. So cortisol is produced. Cortisol is good at getting through the placenta and into the body of the pup. A stressed mother means that the pup is exposed to lots of cortisol, which inhibits growth of the fetus. It gets born with a smaller brain. There's evidence the same thing happens with humans as well. And at least in that the effects are irreversible. So what's all this about? When is an animal likely to secrete cortisol? When running for its life. It's got better things to do than worry about long term projects, like growing bones and maintaining an immune system. You don't worry about long-term planning if you're not sure there's going to be a long term. Well, if you're a fetus, and your mother is exposed to stress, you end up less well-developed. The parts of the brain involved in cortisol reception, such as the hippocampus, shown here in this figure, end up particularly small. And that matters. because the hippocampus is the brain region linked to learning and memory, and it [INAUDIBLE] connection to the cerebral cortex and the amygdala. And the hippocampus is involved in a negative feedback system. The cortisol receptors in the hippocampus turn on a molecular brake, which cuts off cortisol production. So if the hippocampus is smaller You have less of a capacity to turn off cortisol. Cortisol is also blamed for atrophy of the hippocampus in people who have experienced severe stress, such as in post-traumatic stress disorder. Combat veterans of the Vietnam War With post-traumatic stress disorder, showed a 20% reduction in the volume of their hippocampus, compared with veterans who suffered no such symptoms. During stress, the hippocampus is particularly important in the prior memories and have a great influence on enhancing, suppressing or independently generating a stress response. Working properly cortisol and all these receptors in the hippocampus, help you retrieve useful memories quickly in times of trouble, so you don't delay before taking action. Too much cortisol for too long, and you keep retrieving bad memories, and reliving the same stressful situations over and over again, which is the major symptom of post-traumatic stress disorder. It seems that humans have, throughout their life history, suffered from a lot of stress. First there were lions, and tigers and bears, then there were other humans, with pointy, metal objects and now there's deadlines and traffic jams, and bankruptcy. Stress can be rough on the body. It can produce depression, anxiety, increased sensitivity to illness, and it can even shorten your life expectancy. The philosopher Hobbes wrote that human life without civilization was solitary, poor, nasty, brutish and short. It probably was poor, nasty, brutish and short, but seldom has it been solitary. That's likely a modern stress, and perhaps the worst we face, because it's unnatural for our species. But otherwise it's, it's probably wrong to think that our modern life produces a lot of unnatural, prolonged stresses. In prehistoric times, we only had short-lived stresses we could easily cope with. We share 94% of our genome with the baboons, and the work of Robert Sapolsky has helped make a troop of baboons in East Africa key models for how we cope with stress. There's a quote from him, in a, in a speech he gave recently. If you're the gazelle, you don't have a very complicated emotional life, despite being a social species. But primates are just smart enough that they can think their bodies into working differently. If you live in a baboon troop in the Serengeti, you only have to work three hours a day for your calories, and predators don't mess with you much. Well, that means that you've got nine hours of free time every day to devote to generating psychological stress towards other animals in your troop. They're just like us. They're not getting done in by predators and famines. They're getting done in by each other. Like every other mammal, baboons, suffer from immune suppression by cortisol. And just like us, the biology of baboons is often at the mercy of their behavior. A young male baboon joins a new troop, tries to rise up the hierarchy. It's going to be very aggressive, under a lot of stress and it'll have the high cortisol to prove it. Its immune system will bear the brunt of this, and aside fewer white blood cells and more illnesses, it's also going to experience furring up of the arteries. Furring of the arteries is often linked with high cortisol and a suppressed immune system. Suggesting to some that fatty [INAUDIBLE] and clogged arteries may be caused by inflammation from bacterial infections as well as diet. Among monkeys at the zoo, the ones at the bottom of the pecking order, who get bullied a lot, they have the most cortisol and worst immune systems, and the most furred up [INAUDIBLE] arteries. And they had brains low in serotonin. Now, remember, I talked about serotonin last week, and I mentioned that high status animals have high serotonin. Well, we're just like monkeys. The lower we are in the pecking order, the less control we have over our lives, and the more stress we feel. The lower our serotonin is going to be, and the higher our cortisol. And in fact, the studies with monkeys were done after some really big studies in America and Britain, found that the status of a person's job was more likely to predict their likelihood of a heart attack. But obesity, smoking or high blood pressure. If you're at the top of the heap, you're a boss and are fat you're less likely to suffer a heart attack than if you're thin and work as a janitor. That means the status of your job is more important than all the physiological causes, such as obesity preferred by the magical profession. So, what's going on? Just as with the monkeys, it's been shown that cortisol levels in your blood respond not to workload, but to the degree to which you're ordered about by other people. When you feel you don't have control of your life, you get stressed. Stress means cortisol, and cortisol means a suppressed immune system. [SOUND]
